Experimental allergic encephalomyelitis (EAE) serves as a model for the study of therapies for demyelinating disease of the central nervous system. Its similarity to multiple sclerosis (MS) lies not only in clinical features and pathology but, more importantly, like MS susceptibility to EAE is limited closely to IR genes of the major histocompatibility complex (MHC). It has been shown that treatment in vivo with monoclonal antibody directed against the cell surface of the susceptibility gene product the IA antigen can prevent the induction of acute EAE and reverse the course of chronic EAE. Similar observations have been made in other autoimmune diseases, wherein susceptibility was linked to the IR genes of the MHC. While the mechanism of action of anti IA antibody is not known, there is sufficient evidence to indicate that part of the suppression is induced by the generation of suppressor cells. This proposal attempts to characterize the cellular nature of suppression. Using adoptive transfer systems it hopes to define the nature of suppression of acute and chronic EAE following treatment in vitro and in vivo with monoclonal antibody directed towards IR gene products. In addition these experiments will study the genetic specificity of suppression using various inbred strains of mice and antigenic specificities using autoantigens and synthetic antigens whose immune responsiveness is under IR gene control. At the present time the mechanism by which IR genes confer susceptibility to autoimmune disease is not known. Understanding mechanisms by which antibody to IR gene products regulate autoimmune disease might lead to an improved knowledge of the pathogenesis of such diseases.